Robinson stereochemistry

If you don t see why the stereochemistry should be as 1 have drawn it, 1 suggest you make a model of 332A and discover for yourself There is a simple synthesis of 332A (X = OTs) from the Robinson annelation (frame 117) product 332B. 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Robinson, P.L., Barry, C.N., Kelly, J.W., and Evans, S.A., Diethoxytriphe-nylphosphorane a mild, regioselective cyclodehydrating reagent for conversion of diols to cyclic ethers. Stereochemistry, synthetic utility, and scope, /. Am. Chem. Soc., 107, 5210, 1985. 

See Addendum I in G. N. Burkhardt, Arthur Lapworth and Others, typescript in Robert Robinson papers, Library of the Royal Society of London. Students preparing the diplome d etudes superieures in chemistry at the Ecole Normale Superieure in the 1920s were asked to discuss questions in the oral part of the juried examination. Topics included catalysis, stereochemistry of salt complexes, and the origins of atomic notation. See bound copy of examination memoirs, presented to Albert Kirrmann, in archives of Ecole Normale Superieure Laboratoire de Chimie. 

Robinson, M. J. T. Organic Stereochemistry, Oxford University Press, Oxford, 2002. 

Stevens and Lee (28) have reported an elegant synthesis of coccinelline (69). Treatment of 66 at pH=l gave intermediate 67 which was then treated with dimethyl acetone dicarboxylate at pH=5.5 to give a single tricyclic isomer, the ketodiester 68, in 75% yield. Compound 68 was then converted into coccinelline (59). This result shows that the Robinson-Schopf reaction (29, 30) can take place with a remarkable control of stereochemistry. 

This principle is often applied to molecules. If a nucleophile is joined to the carbonyl group it is to attack by a short chain of covalent bonds, it may be able to reach only one side of the carbonyl group. An example from a familiar reaction concerns the Robinson annelation. The first step, Michael addition, creates a stereo genic centre but no relative stereochemistry. It is in the second step—the aldol cyclization—that the stereochemistry of the ring junction is decided. 

The method used by Coates and Robinson" involved the copper-catalysed decomposition of trans,trans-farnesyl diazoacetate (4) to the cyclopropyl-lactone (5) having the stereochemistry shown. This was transformed into the cis-aldehyde-ester (6) by standard methods. Base epimerization gave the more stable transcompound (7). A Wittig reaction between the trans-aldehyde-ester (7) and the phosphorane (8), followed by lithium aluminium hydride reduction, yielded presqualene alcohol (1) as the major product accompanied by the minor isomer (9). 

Agami, C., Meynier, F., Puchot, C., Guilhem, J., Pascard, C. Stereochemistry - 59. New insights into the mechanism of the proline-catalyzed asymmetric Robinson cyclization structure of two intermediates. Asymmetric dehydration. Tetrahedron 1984,40,1031-1038. 

The stereochemistry of teloidine, the alkamine of meteloidine, has been elucidated as far as the vicinal hydroxy groups are concerned by its Robinson synthesis from cis-dihydroxysuccinic dialdehyde (68). Their relative positions to the nitrogen, however, have been revealed only by... 

H 4.67%, O 31.76%. From the heart-wood of logwood (Haematoxylon campechianum Linn., Leguminosae) Chev-reul, Ann. Chim. Phys. 82, 54, 126 (1810). Structure Perkin, Robinson, J. Chem. Soc. 93, 489 (1908). Synthesis Dann, Hofmann, Angew, Chem, 75, 1125 (1963) Morsingh, Robinson, Tetrahedron 26, 281 (1970) Kirkiacharian, Billet, Bull. Soc. Chim. France 1972, 3292. Review Robinson, ibid. 1958, 125. Stereochemistry Craig et ah, J. Org. Chem. 30, 1573 (1965). 

There are very many books on stereochemistry. The most comprehensive is probably E. L. Eliel and S. H. Wilen, Stereochemistry of Organic Compounds, Wiley Interscience, Chichester, 1994. But you may find this too comprehensive at this stage. A more accessible introduction is the Oxford Primer Organic Stereochemistry, M. J. T. Robinson, OUP, Oxford, 2001. 

Stevens RV, Lee AWM (1979) Stereochemistry of the Robinson-Schoepf reaction. A stereospecific total synthesis of the ladybug defense alkaloids precoccinelline and coccinelline. J Am Chem Soc 101 7032-7035... 

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